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Petah Tikva, Israel

Meivar-Levy I.,Endocrine Institute
Methods in molecular biology (Clifton, N.J.) | Year: 2010

Regenerative medicine aims at producing new cells for repair or replacement of diseased and damaged tissues. Embryonic and adult stem cells have been suggested as attractive sources of cells for generating the new cells needed. The leading dogma was that adult cells in mammals, once committed to a specific lineage, become "terminally differentiated" and can no longer change their fate. However, in recent years increasing evidence has accumulated demonstrating the remarkable ability of some differentiated cells to be converted into a different cell type via a process termed developmental redirection or adult cells reprogramming. For example, abundant human cell types, such as dermal fibroblasts and adipocytes, could potentially be harvested and converted into other, medically important cell types, such as neurons, cardiomyocytes, or pancreatic beta cells. In this chapter, we describe a method of activating the pancreatic lineage and beta-cells function in adult human liver cells by ectopic expression of pancreatic transcription factors. This approach aims to generate custom-made autologous surrogate beta cells for treatment of diabetes, and possibly bypass both the shortage of cadaveric human donor tissues and the need for life-long immune-suppression.

Melamud L.,Multiple Sclerosis Center | Golan D.,Multiple Sclerosis Center | Luboshitzky R.,Endocrine Institute | Luboshitzky R.,Technion - Israel Institute of Technology | And 3 more authors.
Journal of the Neurological Sciences | Year: 2012

Background: Sleep disruption and fatigue are common in Multiple Sclerosis (MS). Melatonin is one of the major regulators of sleep-wake cycle. The role of melatonin in MS-related sleep disturbances and fatigue as well as the interaction between melatonin and Interferon beta (IFN-β) treatment were the subject of this study. Objective: To assess the influence of IFN-β treatment on melatonin secretion, fatigue and sleep characteristics in patients with MS. Methods: 13 MS patients and 12 healthy controls participated. Fatigue was evaluated using the Fatigue Impact Scale (FIS), sleep was assessed by actigraphy and day/night levels of 6-sulphatoxy-melatonin (6-SMT) in urine were determined using a highly specific ELISA assay. Results: Naïve MS patients demonstrated significantly decreased levels of 6-SMT and disrupted circadian regulation of its secretion, which were increased with IFN-β treatment, in association with improved fatigue. Sleep Efficiency was significantly lower in the MS group compared to controls. Conclusion: Our findings suggest dysregulation of Melatonin secretion in MS, which may be influenced by IFN-β treatment. The results call for further characterization of the role of neuro-hormones such as melatonin in MS, and their cross-regulation with immune-mediators. © 2011 Elsevier B.V. All rights reserved.

Fulcher G.,University of Sydney | Singer J.,Endocrine Institute | Castaneda R.,Clinical Epidemiology Research Unit | Fraige Filho F.,University of Sao Paulo | And 3 more authors.
Journal of Medical Economics | Year: 2014

Objectives: To understand the impact of nocturnal and daytime non-severe hypoglycemic events on healthcare systems, work productivity and quality of life in people with type 1 or type 2 diabetes.Methods: People with diabetes who experienced a non-severe hypoglycemic event in the 4 weeks prior to the survey were eligible to participate in a nocturnal and/or daytime hypoglycemia survey. Surveys were conducted in Argentina, Australia, Brazil, Israel, Mexico and South Africa.Results: In total, 300 respondents were included in nocturnal/daytime hypoglycemia surveys (50/participating country/survey). All respondents with type 1 diabetes and 68%/62% (nocturnal/daytime) with type 2 diabetes were on insulin treatment. After an event, 25%/30% (nocturnal/daytime) of respondents decreased their insulin dose and 39%/36% (nocturnal/daytime) contacted a healthcare professional. In the week after an event, respondents performed an average of 5.6/6.4 (nocturnal/daytime) additional blood glucose tests. Almost half of the respondents (44%) reported that the event had a high impact on the quality of their sleep. Among nocturnal survey respondents working for pay, 29% went to work late, 16% left work early and 12% reported missing one or more full work days due to the surveyed event. In addition, 50%/39% (nocturnal/daytime) indicated that the event had a high impact on their fear of future hypoglycemia.Conclusions: The findings suggest that nocturnal and daytime non-severe hypoglycemic events have a large financial and psychosocial impact. Diabetes management that minimizes hypoglycemia while maintaining good glycemic control may positively impact upon the psychological wellbeing of people with diabetes, as well as reducing healthcare costs and increasing work productivity. © 2014 Informa UK Ltd.

Ishay A.,Endocrine Institute | Ishay A.,Technion - Israel Institute of Technology | Pollak Y.,Haemek Medical Center | Chervinsky L.,Haemek Medical Center | And 3 more authors.
Endocrine Practice | Year: 2010

Objective: To assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction. Methods: In this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal serum free thyroxine (FT 4) and free triiodothyronine (FT 3) in the presence of high (subclinical hypothyroidism), or low-suppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT 4, FT 3, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroidism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements. Results: The study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 ± 5.6 cm/s vs 15.7 ± 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 ± 10.7 cm/s vs 21.9 ± 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P<.001] and 53% vs 15%; [P<.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity. Conclusion: We have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction. © 2010 AACE.

Guy A.,Endocrine Institute | Guy A.,Tel Aviv University | Hirsch D.,Endocrine Institute | Hirsch D.,Tel Aviv University | And 10 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: The presence of cervical lymph node metastases is a strong predictor of persistent disease in papillary thyroid cancer (PTC).Objective: The objective of the study was to investigate factors associated with improved outcome in patients with PTC and lymph node metastases.Design: Retrospective Cohort Setting The study was conducted at a tertiary university-affiliated medical center.Patients: Patients treated for PTC and N1 disease since 1995 participated in the study. Partial thyroidectomy, distant metastases, and poor differentiation were the exclusion criteria.Interventions: The intervention was a data search of the Thyroid Registry.Main Outcome Measures: Significant association of clinical and disease-related factors with persistent disease was measured.Results: Of 800 patients treated for PTC during the study period, 182 (69% female; mean age at diagnosis 46.5± 15 y) had N1 disease (47% N1a, 53% N1b). Most (93.4%) had a classical/follicular variant; 65% had T1-2 disease; and 42.6% had extrathyroid extension. All patients were treated with total thyroidectomy and radioactive iodine (mean first dose 147± 26 mCi). Lateral neck dissection was performed in 53% patients. Mean follow-up was 9.2± 4.5 years. On regression analysis, factors significantly and independently associated with persistent disease at 1 year (94 of 182, 52%; 40% of N1a group, 59% of N1b group) were primary tumor size, focality, and extrathyroid extension and at the last follow-up (62 of 182, 34%; 27% of N1a group, 33% of N1b group), primary tumor size, 1-year stimulated thyroglobulin level, and cumulative I131 dose. Stimulated thyroglobin less than 2.1 ng/mL at 1 year predicts the absence of disease at the last follow-up with an 86% negative predictive value.Conclusion: Patients with PTC and N1 disease treated with total thyroidectomy and radioactive iodine have a significant risk of persistent disease at early and late follow-up. The extension of the primary tumor at diagnosis appears to be the only significant predictor of persistency in these patients. Copyright © 2014 by the Endocrine Society.

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